title: A novel small molecule methyltransferase is important for virulence in Candida albicans.
abstract: Candida albicans is an opportunistic pathogen capable of causing life-threatening infections in immunocompromised individuals. Despite its significant health impact, our understanding of C. albicans pathogenicity is limited, particularly at the molecular level. One of the largely understudied enzyme families in C. albicans are small molecule AdoMet-dependent methyltransferases (smMTases), which are important for maintenance of cellular homeostasis by clearing toxic chemicals, generating novel cellular intermediates, and regulating intra- and interspecies interactions. In this study, we demonstrated that C. albicans Crg1 (CaCrg1) is a bona fide smMTase that interacts with the toxin in vitro and in vivo. We report that CaCrg1 is important for virulence-related processes such as adhesion, hyphal elongation, and membrane trafficking. Biochemical and genetic analyses showed that CaCrg1 plays a role in the complex sphingolipid pathway: it binds to exogenous short-chain ceramides in vitro and interacts genetically with genes of glucosylceramide pathway, and the deletion of CaCRG1 leads to significant changes in the abundance of phytoceramides. Finally we found that this novel lipid-related smMTase is required for virulence in the waxmoth Galleria mellonella, a model of infection.
authors.affiliation: Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto , 160 College St., Toronto, M5S 3E1, Canada.
authors.forename: Elena
authors.initials: E
authors.lastname: Lissina
authors.forename: David
authors.initials: D
authors.lastname: Weiss
authors.forename: Brian
authors.initials: B
authors.lastname: Young
authors.forename: Antonella
authors.initials: A
authors.lastname: Rella
authors.forename: Kahlin
authors.initials: K
authors.lastname: Cheung-Ong
authors.forename: Maurizio
authors.initials: M
authors.lastname: Del Poeta
authors.forename: Steven G
authors.initials: SG
authors.lastname: Clarke
authors.forename: Guri
authors.initials: G
authors.lastname: Giaever
authors.forename: Corey
authors.initials: C
authors.lastname: Nislow
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D002193:Cantharidin / Q000494:pharmacology; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002518:Ceramides / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017353:Gene Deletion; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009036:Moths / Q000382:microbiology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014774:Virulence
chemical_list: D002518:Ceramides; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C570204:Crg1 protein, S cerevisiae; D008780:Methyltransferases; D002193:Cantharidin